Systemic Disease Research Articles

4-Octyl itaconate inhibits inflammation via the NLRP3 pathway in neuromyelitis optica spectrum disorders.

Neuromyelitis optica spectrum disorders (NMOSD) are rare inflammatory astrocytic diseases of the central nervous system (CNS). The roles of immune response gene-1 (IRG1) and the IRG1-itaconic acid-NLRP3 inflammatory pathway in the pathogenesis of NMOSD and the effects of 4-octyl itaconate (4-OI) on the NLRP3 inflammatory pathway in NMOSD are unclear. This study aimed to determine the role of IRG1 and the activation status of the NLRP3 inflammatory pathway in acute-onset NMOSD and to investigate the inhibitory effects of 4-OI on NLRP3 inflammasome activation via the IRG1-itaconic acid-NLRP3 pathway in monocytes and macrophages by using in vitro models. Peripheral blood mononuclear cells (PBMCs) and serum were collected from patients with acute NMOSDs and healthy controls (HC), followed by monocyte typing and detection of the expression of NLRP3-related inflammatory factors. Subsequently, the effects of 4-OI on the IRG1-itaconic acid-NLRP3 pathway were investigated in peripheral monocytes from patients with NMOSD and in macrophages induced by human myeloid leukemia mononuclear cells (THP-1 cells) via in vitro experiments. Patients with acute NMOSD exhibited upregulated IRG1 expression. In particular, the upregulation of the expression of the NLRP3 inflammasome and proinflammatory factors was notable in monocytes in acute NMOSD patients. 4-OI inhibited the activation of the IRG1-itaconic acid-NLRP3 inflammatory pathway in the PBMCs of patients with NMOSD. 4-OI could effectively inhibit NLRP3 signaling, leading to the inhibition of proinflammatory cytokine production in patients with NMOSD-derived PBMCs and in a human macrophage model. Thus, 4-OI and itaconate could have important therapeutic value for the treatment of NMOSD in the future.

The risk for ophthalmological conditions in ulcerative colitis: A population-based case-control study. Is silica dust-exposure associated with inflammatory eye disease?

To study the risk for eye diseases in individuals with Ulcerative Colitis (UC), and to assess whether silica dust-exposure could contribute to the development of inflammatory eye diseases. A case-control study was conducted using a patient register processed by the National Board of Health and Welfare (NBHW) and Statistics Sweden. Cases were diagnosed with UC between 2007 and 2016. Matching was done with two random controls having the same age, sex and county of residence, without a systemic inflammatory disease. Using a job-exposure matrix, cases and controls were assessed for work-related silica dust exposure. The risk for eye disease was estimated by Cox regression analysis with calculation of Hazard Ratio (HR). A total of 58 989 individuals were included, comprising 19 663 cases and 39 326 controls. The sex distribution was similar. Overall, individuals with UC had an increased risk for eye disease, specified in ICD 10 chapter VII (H00-H59) with HR 1.25 (CI 1.20-1.32). The highest HR on block-level for cases was 1.52 (CI 1.36-1.70), (H15-H22), which includes episcleritis, keratitis and anterior uveitis. The risk for ocular disease was higher in silica dust-exposed than non-exposed with a HR of 1.44 (CI 1.16-1.78) and 1.25 (CI 1.19-1.31), respectively. Among cases, the risk for iridocyclitis (H20) was further elevated by silica dust exposure, with HR of 3.84 (CI 1.64-8.97) in exposed compared to 1.94 (1.57-2.41) in non-exposed. UC is associated with an increased risk for eye diseases, including inflammatory conditions. Our findings highlight that silica dust-exposure may be of importance in the pathogenesis of uveitis.

Choroidal thickness and retinal vascular changes in patients with lichen planus: an inflammatory disease beyond the skin.

Lichen planus (LP) is a common inflammatory condition of unknown etiology that commonly affects the skin and mucous membranes. Optical coherence tomography angiography (OCTA) is a noninvasive technique for identifying early retinal vascular impairment in systemic disease without clinical damage by imaging deep and superficial capillary networks. To assess the impacts of LP on the choroid and assess vascular changes in retinal capillary density using OCTA. This single-center prospective case-control study included 30 therapeutic-naïve LP patients and 30 age and sex-matched healthy individuals. All study subjects underwent a complete ophthalmological examination, including best-corrected visual acuity (BCVA) measurement using a Snellen chart, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, and fundus examination. They were then examined using spectral domain OCT and choroidal thickness was measured. The vessel density of the superficial and deep capillary networks was measured and assessed using OCTA. Patients had significantly thicker choroidal and retinal thickness than controls, with subfoveal, nasal, and temporal areas showing a significant difference. A significantly higher vascular density in the superficial capillary plexus, particularly in the nasal perifoveal area, was found compared to the control group. Significantly, higher vascular density in the deep capillary plexus in the parafoveal area compared to controls was reported. Significant correlations were found between visual acuity and IOP, and age, duration of disease, and severity of disease. This study is the first to reveal that LP patients exhibit choroidal changes and retinal vascular alterations compared to healthy controls.

Progress in progressive pulmonary fibrosis: biomarkers of systemic sclerosis-associated interstitial lung disease.

Progress in progressive pulmonary fibrosis: biomarkers of systemic sclerosis-associated interstitial lung disease.

ASSESSMENT OF TREATMENT OUTCOMES AND SOME RISK FACTORS FOR MORTALITY OF COMMUNITY-ACQUIRED PNEUMONIA CAUSED BY STAPHYLOCOCCUS AUREUS IN THE ELDERLY POPULATION

Objectives: Community-acquired pneumonia is a notable contributor to mortality from infectious diseases on a worldwide scale, especially in the older population. Staphylococcus aureus is a prevalent infection known to cause severe pneumonia, often leading to a high incidence of complications and fatality. The study's objective was to assess the treatment outcomes and some factors associated with mortality rates of Staphylococcus aureus pneumonia in older people. Subjects and method: A cross-sectional study was conducted with 93 patients diagnosed with Staphylococcus aureus pneumonia admitted to Can Tho Central General Hospital from April 2021 to May 2023. Results: The research results showed clinical outcomes including 30-day all-cause death rates and pneumonia-related complications were slightly higher in the age group over 60 compared to those aged 60 and under, but the difference was not statistically significant. After performing multivariate analysis, it was found that heart failure (OR = 5.68, 95% CI: 1.01-32.1, p = 0.049) and central nervous system disease (OR = 5.26, 95% CI: 1.32-20.9, p = 0.018) were found to be independent factors that increased the mortality rate in individuals aged over 60. Conclusion: Clinical practitioners should evaluate and manage comorbidities regarding heart failure and central nervous system diseases during treatment of Staphylococcus aureus pneumonia due to its elevated fatality rate, especially in old patients.

Comparison of dmft and behavior rating scores between children with systemic disease and healthy children at the first dental visit

PurposeTo evaluate and compare oral health and behavior scores at the first dental visit and dental treatment need using general anesthesia/sedation (GA/S) of children with systemic diseases (SD) and healthy children.MethodsData were obtained from healthy children (n = 87) and children with SD (n = 79), aged 4 to 6 years, presenting to a hospital dental clinic for a first dental examination. The total number of decayed, missing and filled teeth (dmft), dental behavior score using Frankl Scale, and dental treatment need using GA/S were recorded. Chi-square / Fisher’s exact test and Mann–Whitney U tests were used for statistical analyses.ResultsThe patients with SD were diagnosed with cardiac disease (61%), renal disease (9%), and pediatric cancers (30%). The median dmft values of the SD group (3.00) were significantly lower than those of healthy children (5.00) (p = 0.02) and healthy children exhibited significantly more positive behavior (90.8%) than children with SD (73.4%) (p = 0.002). The number of patients needing GA/S for dental treatment did not differ significantly between the two groups (p = 0.185). There was no relationship between dental treatment need with GA/S and dental behavior scores of the patients (p = 0.05). A statistically significant relationship was found between the patients’ dmft scores and the need for dental treatment using GA/S; and the cut-off value was found to be dmft > 4 for the overall comparisons.ConclusionThe presence of chronic disease in children appeared to affect the cooperation negatively at the first dental visit compared to healthy controls, however, it did not affect the oral health negatively. Having a negative behavior score or SD did not necessitate the use of GA/S for dental treatment.

ИЗУЧЕНИЕ ВЛИЯНИЯ ОРТОПЕДИЧЕСКИХ ТОВАРОВ НА ТОВАРООБОРОТ АПТЕЧНЫХ ОРГАНИЗАЦИЙ

Proper pharmaceutical care to the population is the most important task of our state. At the same time, the main role in resolving this issue belongs to retail pharmacy organizations, ensuring the availability of medicines and other pharmaceutical products for consumers. However, along with the need to provide timely and high-quality pharmaceutical services, retail pharmacy organizations are currently faced with a number of serious economic problems, among which the most pressing is the search for ways to increase competitiveness. As practice shows, one of the ways to solve this problem is to expand the functionality and range of pharmacy organizations, which, in particular, implies the creation of new and/or development of departments within them. One of the promising departments of a modern pharmacy organization is the orthopedic department. The market for orthopedic products has a noticeable and steady upward trend; the number of actual and potential consumers of these products, as well as the volume of their sales, increases every year. Orthopedic products for people with diseases of the musculoskeletal system are in particular demand, and demand is also growing among the group of consumers purchasing these products for sports and for the purpose of disease prevention. At the same time, an important issue is the organization of rational placement and comprehensive information to potential consumers about the properties, advantages and necessity of such goods. Integrated sales of medicines, other pharmaceutical products and orthopedic products can create an additional competitive advantage for a pharmacy organization in comparison with others and improve the economic and financial performance of the retail chain. The purpose of this study was to study the influence of orthopedic products on the turnover indicators of a pharmacy organization and to study the approaches used in practice for their placement in the sales area of a pharmacy. As a result of the research, comparative data on the influence of orthopedic products on the turnover indicators of a pharmacy organization were obtained and the approaches used in practice to their placement in the sales area of pharmacy organizations were studied. It has been established that orthopedic products occupy a significant portion of sales in the total turnover of pharmacy organizations. At the same time, the best economic indicators in this regard were demonstrated by a pharmacy that has a separate orthopedic department, which allows us to consider it expedient to create specialized units in this area in a pharmacy organization.

Role of miRNAs in neurovascular injury and repair.

MicroRNAs (miRNA) are endogenously produced small, non-coded, single-stranded RNAs. Due to their involvement in various cellular processes and cross-communication with extracellular components, miRNAs are often coined the "grand managers" of the cell. miRNAs are frequently involved in upregulation as well as downregulation of specific gene expression and thus, are often found to play a vital role in the pathogenesis of multiple diseases. Central nervous system (CNS) diseases prove fatal due to the intricate nature of both their development and the methods used for treatment. A considerable amount of ongoing research aims to delineate the complex relationships between miRNAs and different diseases, including each of the neurological disorders discussed in the present review. Ongoing research suggests that specific miRNAs can play either a pathologic or restorative and/or protective role in various CNS diseases. Understanding how these miRNAs are involved in various regulatory processes of CNS such as neuroinflammation, neurovasculature, immune response, blood-brain barrier (BBB) integrity and angiogenesis is of empirical importance for developing effective therapies. Here in this review, we summarized the current state of knowledge of miRNAs and their roles in CNS diseases along with a focus on their association with neuroinflammation, innate immunity, neurovascular function and BBB.

A real-world disproportionality analysis of the FDA adverse event reporting system events for ibuprofen

ABSTRACT Introduction Ibuprofen is commonly used as an over-the-counter (OTC) antipyretic and analgesic. As the frequency of its use has increased, there has been a corresponding increase in reports of associated adverse events (AEs). However, these events have not been systematically reported in the literature. Meanwhile, the importance of effective pharmacovigilance in evaluating the benefits and risks of drugs is being recognized. Methods The data was obtained indirectly from FAERS using the OpenVigil 2 database, lexically mapped using software such as MySQL, Microsoft Excel, and the R language, and then subjected to four more rigorous algorithms to detect risk signals associated with ibuprofen AEs. Results By analyzing data from the past 18 years, 878 ibuprofen-related AEs were identified as primary AEs. Notably, unexpected reproductive system and breast diseases, etc., which were unexpected, were observed as important system organ classes (SOCs) associated with ibuprofen. Among the 651 preferred terms (PTs) that simultaneously satisfy the four arithmetic methods, renal tubular acidosis and lip oedema are proposed as new signals for ibuprofen AEs. Conclusion This study explores the important and valuable potential AEs and ADRs of ibuprofen at the SOC and PT levels, respectively. To provide a reference on decision-making for ibuprofen to promote rational clinical dosing.

Tocilizumab in the treatment of hyperferritinemic syndrome and capillary leak syndrome secondary to rheumatoid arthritis: Case report and literature review.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, which is mainly characterized by joint swelling, pressure pain and joint destruction. Some patients may suffer from a variety of serious complications, which require prompt diagnosis and treatment. Otherwise, the patient condition may deteriorate rapidly, leading to premature death. We reported a case of RA combined with hyperferritinemic syndrome and capillary leak syndrome (CLS) that was successfully treated with tocilizumab (TCZ), with the aim of improving diagnostic ideas for clinicians and consequently improving the diagnosis and treatment of the hyperferritinemic syndrome and CLS. A 55-year-old female patient was admitted to the Department of Infectious Diseases of our hospital due to "recurrent fever for more than 1 month and aggravation for 3 days." The patient was diagnosed with fever of unknown origin (lung infection?) and received anti-infective therapy with large encirclement of anti-bacterial, antifungal and empirical anti-tuberculosis successively during hospitalization in the Department of Infectious Diseases. Yet her condition continues to progress. The patient was eventually diagnosed with RA combined with hyperferritinemic syndrome and CLS. Then she received glucocorticoids (GC) (160 mg qd) combined with intravenous immunoglobulin (IVIG, 20 g/d, for 3 days). We considered that the patient also had an overwhelming proinflammatory cytokine storm, so she received a strong anti-inflammatory treatment with TCZ (400 mg qm). The patient symptoms and follow-up chest CT showed significant improvement following treatment. TCZ has good efficacy in the treatment of RA combined with hyperferritinemic syndrome and CLS and is expected to be a promising treatment.

The Frequency of Celiac Disease and Its Association with Infertility in Women Attending Infertility Clinics: A Case-Control Study in Southern Iran

Background: Celiac disease (CD) is a multifactorial systemic disease that causes enteropathy and can lead to a wide spectrum of disorders related to infertility. Objectives: This case-control study aimed to evaluate the frequency of celiac disease (CD) and its association with infertility in women. Methods: This study was conducted on women referred to Ghadir Mother and Child Hospital in Shiraz. Women with infertility served as the case group, while fertile women comprised the control group. Blood samples were collected from participants, and tissue anti-transglutaminase (Anti-TTG Ab) levels were measured. Patients with elevated Anti-TTG Ab levels were referred for duodenal biopsy. Results: One hundred subjects were enrolled in the case group and 200 in the control group. Eight patients in the case group tested positive for serology, and four of these had duodenal biopsies confirming CD. In the control group, one individual tested positive for serology, but the duodenal biopsy was negative (P for between-group differences: 0.001 for serology and 0.012 for biopsy results). There was a significant association between high levels of Anti-TTG Ab and infertility (odds ratio = 17.30, 95 % CI: 2.13 - 140.39), which remained even after adjusting for age and body mass index (odds ratio = 9.92, 95 % CI: 1.17 - 84.21). Conclusions: The frequency of CD was higher among infertile women compared to fertile women. Increased levels of Anti-TTG Ab were independently associated with infertility.

Comparative evaluation of the diagnostic and prognostic performance of CNSide™ versus standard cytology for leptomeningeal disease

Abstract Background This retrospective study compares real-world performance of cerebrospinal fluid (CSF) CNSide™ versus cytology in leptomeningeal disease (LMD). Methods: Consecutive patients with suspected LMD who underwent lumbar punctures for CSF cytology and CNSide™ from January 2020 to December 2022 were reviewed. LMD was classified by EANO criteria. Descriptive statistics, confusion matrix, Kaplan Meier curves, and Cox proportional regression were used. Results Median age for 87 evaluable patients was 63 years (range:23-93); 82 (94%) met EANO criteria for possible/probable/confirmed LMD (EANO/LMD). The commonest primary cancers were breast (36,44.0%) and lung (34,41.5%). Primary lung harbored actionable mutations in 18 (53.0%); primary breast expressed hormone receptors in 27 (75%) and HER2 amplification in 8 (22%). Uncontrolled systemic disease was detected in 35 (40%), while 25 (46%) received systemic therapy with medium/high CNS penetrance at LMD diagnosis. Median time from initial cancer to LMD diagnosis was 31 months (range:13-73). LMD was confirmed by CSF cytology in 23/82 (28%), all identified by CNSide™. CNSide™ identified 13 additional cases (36/82,43.9%), increasing diagnostic yield by 56.5%. Median overall survival (mOS) was 31 weeks (95%CI:21-43), significantly worse for CNSide™ positive versus negative: 4.0 versus 16.0 weeks, respectively (HR=0.50,p=0.010). While survival since LMD diagnosis did not differ by histology, time to LMD diagnosis from initial cancer diagnosis was longer for breast (48.5 months,IQR:30.0-87.5) versus lung (8 months,IQR:0.5-16.0) cohorts. mOS was longer for patients eligible for intrathecal chemotherapy (HR:0.189, 95%CI:0.053-0.672, p=0.010). Conclusions This retrospective, real-world analysis of CNSide™ showed increased sensitivity versus cytology and provided clinically relevant molecular CSF analyses.

Utilization of aggregation‐induced emission materials in urinary system diseases

AbstractWith the development of aggregation‐induced emission (AIE) materials, the drawbacks of conventional fluorescence materials subjected to aggregation‐caused quenching (ACQ) have been resolved. This has allowed for the improvement of novel AIE fluorescent materials that exhibit enhanced photostability, a higher signal‐to‐noise ratio, and better imaging quality. Meanwhile, the enhanced phototherapeutic effect of AIE materials has garnered widespread attention in the realm of tumor treatment. The distinct physiological and anatomical characteristics of the urinary system make it suitable for the use of AIE materials. Additionally, AIE‐based phototherapy provides a superior solution to deal with the weaknesses of conventional treatments for urologic neoplasms. In this review, the scientific advancement on the use of AIE materials in urinary system diseases since the emergence of the AIE concept is reviewed in detail. The review highlights the promise of AIE materials for biomarkers detection, fluorescence imaging (FLI) in vivo and in vitro, AIE‐based phototherapy, and synergistic therapy from both diagnostic and therapeutic viewpoints. It is firmly believed that AIE materials hold immense untapped potential for the diagnosis and treatment of urologic disease, as well as all diseases of the human body.

Efficacy and safety of Piwei Peiyuan Prescription in the treatment of chronic atrophic gastritis: A multicenter, double-blind, double-simulated, randomized, controlled clinical trial.

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ± 1.08 vs 3.00 ± 1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ± 1.43 vs 1.69 ± 1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ± 1.13 vs 2.80 ± 0.99, P = .022), preference for warmth and pressure (1.44 ± 1.06 vs 1.36 ± 1.10, P = .041), and poor appetite and indigestion (0.78 ± 0.66 vs 1.32 ± 0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety.

The impact of serum uric acid on psoriasis: NHANES 2005–2014 and Mendelian randomization

Background:Psoriasis is a chronic systemic inflammatory disease, and hyperuricemia is a common comorbidity in patients with psoriasis. However, the exact relationship between uric acid levels and psoriasis remains unclear. This study aimed to explore the association between uric acid levels and psoriasis.Methods:Observational study participant data (≥16 years, n = 23,489) from NHANES 2003–2014. We conducted analyses using a weighted multiple logistic regression model. Genetic data sets for uric acid levels and psoriasis were obtained from the IEU database. We selected genetically independent loci closely associated with serum uric acid levels as instrumental variables and performed Mendelian randomization analyses using five complementary methods: inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode.Results:After adjusting for other covariates, the results revealed no significant association between serum uric acid levels and psoriasis (b = 0.999, 95% CI: 0.998, 1.001, p = 0.275). Subgroup analyses stratified by gender and ethnicity showed no significant association between sUA and psoriasis in any of the subgroups. Furthermore, the MR analysis involved the selection of 227 SNPs that were associated with both sUA and psoriasis. IVW results demonstrated no causal relationship between sUA and psoriasis (OR = 0.282, 95% CI: -0.094–0.657, p = 0.142).Conclusion:Our study suggests that uric acid levels are not significantly causally related to psoriasis. This finding provides valuable insights for the treatment and prevention of psoriasis, indicating that merely reducing uric acid levels may not be an effective strategy to reduce the risk of psoriasis onset.

Choroid plexus imaging in multiple sclerosis management - a systematic review.

Multiple sclerosis (MS) is a central nervous system (CNS) disease associated with inflammation, demyelination, and neurodegeneration. It affects more than 2 million people globally, and usually occurs in young adults, three-quarters of whom are women. Importantly, accurate diagnosis and treatment are essential, as this disease can lead to the rapid development of disability. The choroid plexus (CP) is a structure widely known as the main cerebrospinal fluid source. However, it is also involved in immune cell trafficking to the cerebrospinal fluid, which is increased in different neurological disorders, particularly those associated with neuroinflammation. As MS is generally thought to be caused by an autoimmune process, it has been suggested that the choroid plexus may play a significant role in its pathogenesis, manifesting via changes in imaging characteristics. Although research regarding this topic has been very limited, the results of the available studies appear promising. To further investigate this subject, we performed a systematic literature review according to the PRISMA 2020 guidelines. The PubMed and Embase databases were searched for relevant articles, and after thorough analysis, 16 studies were included in our review. CP volume was significantly increased in MS patients compared to healthy individuals. Furthermore, some studies found that CP enlargement occurs even before a definite diagnosis. Moreover, a few articles reported correlations between CP volume and brain atrophy, or even disease severity. Our findings show that CP imaging has the potential to become a novel and valuable tool in multiple sclerosis management.

Natural biomimetic nano-system for drug delivery in the treatment of rheumatoid arthritis: a literature review of the last 5 years

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized primarily by synovitis, leading to the destruction of articular cartilage and bone and ultimately resulting in joint deformity, loss of function, and a significant impact on patients’ quality of life. Currently, a combination of anti-rheumatic drugs, hormonal drugs, and biologics is used to mitigate disease progression. However, conventional drug therapy has limited bioavailability, and long-term use often leads to drug resistance and toxic side effects. Therefore, exploring new therapeutic approaches for RA is of great clinical importance. Nanodrug delivery systems offer promising solutions to overcome the limitations of conventional drugs. Among them, liposomes, the first nanodrug delivery system to be approved for clinical application and still widely studied, demonstrate the ability to enhance therapeutic efficacy with fewer adverse effects through passive or active targeting mechanisms. In this review, we provide a review of the research progress on the targeting mechanisms of various natural biomimetic nano-delivery systems in RA therapy. Additionally, we predict the development trends and application prospects of these systems, offering new directions for precision treatment of RA.

Investigation of the molecular mechanism of Smilax glabra Roxb. in treating hypertension based on proteomics and bioinformatics

BackgroundSmilax glabra Roxb. (named tufuling in Chinese, SGR) has both medicinal and edible value. SGR has obvious pharmacological activity, especially in anti-inflammation and treating immune system diseases. This study investigated differential protein expression and its relationship with immune infiltration in hypertension treated with SGR using proteomics and bioinformatics.MethodsN-Nitro L-arginine methyl ester (L-NAME) was used to replicate the hypertension model, with SGR administered by gavage for 4 weeks, and the systolic and diastolic blood pressure in each group of rats was measured using the tail-cuff method every 7 days. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) expressions in each group, followed by the detection of protein expression in rat liver samples using the tandem mass tag (TMT) technique. Additionally, hub targets were output using Cytoscape 3.9.1 software, and ALDH2 expression in the liver and serum in each group of rats was detected by ELISA. Moreover, R4.3.0 software was used to evaluate the relationship between acetaldehyde dehydrogenase 2 (ALDH2) and immune cells, and ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) was performed to identify the components of SGR. Furthermore, the association between components of SGR and ALDH2 was analyzed with molecular docking and LigPlot1.4.5 software.ResultsCompared with the model group (L-NAME), SGR at high and medium doses reduced systolic and diastolic blood pressure while reducing TC, TG, and LDL-C levels and increasing HDL-C levels in hypertensive rats (p &amp;lt; 0.05). Moreover, 92 differentially expressed proteins (DEPs) were identified using TMT. These DEPs participated in peroxisome functioning, fatty acid degradation, and other signaling pathways, with ALDH2 being the core target and correlated with various immune cells. In addition, 18 components were determined in SGR, with 8 compounds binding to ALDH2. Molecular docking was performed to confirm that SGR played a role in hypertension based on the combined action of multiple components.ConclusionIn conclusion, SGR has an antihypertensive effect on L-NAME-induced hypertension, with ALDH2 as its hub target. SGR may regulate neutrophil, regulatory T cell, and other cells’ infiltration by targeting ALDH2, thereby contributing to the treatment of hypertension.

Targeting gut microbiota for immunotherapy of diseases

Targeting gut microbiota for immunotherapy of diseases

Application and Quality of Model-Based Meta-Analysis in Pharmaceutical Research: A Systematic Cross-Sectional Analysis and Practical Considerations.

Model-based meta-analysis (MBMA) can be used in assisting drug development and optimizing treatment in clinical practice, potentially reducing costs and accelerating drug approval. We aimed to assess the application and quality of MBMA studies. We searched multiple databases to identify MBMA in pharmaceutical research. Eligible MBMA should incorporate pharmacological concepts to construct mathematical models and quantitatively examine and/or predict drug effects. Relevant information was summarized to provide an overview of the application of MBMA. We used AMSTAR-2 and PRISMA 2020 checklists to evaluate the methodological and reporting quality of included MBMA, respectively. A total of 143 MBMA studies were identified. MBMA was increasingly used over time for one or more areas: drug discovery and translational research (n = 8, 5.6%), drug development decision making (n = 42, 29.4%), optimization of clinical trial design (n = 46, 32.2%), medication in special populations (n = 15, 10.5%), and rationality and safety of drug use (n = 71, 49.7%). The included MBMA covered 17 disease areas, with the top three being nervous system diseases (n = 19, 13.2%), endocrine/nutritional/metabolic diseases (n = 17, 11.8%), and neoplasms (n = 16, 11.1%). Of these MBMA studies, 138 (96.5%) were rated as very low quality. The average rate of compliance with PRISMA was only 51.4%. Our findings suggested that MBMA was mainly used to evaluate the efficacy and safety of drugs, with a focus on chronic diseases. The methodological and reporting quality of MBMA should be further improved. Given AMSTAR-2 and PRISMA checklists were not specifically designed for MBMA, adapted assessment checklists for MBMA should be warranted.